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In this paper, novel sulfur-containing 1,6-dihydrofuro[3,2-b]pyrazolo[3,4-e][1,4]thiazine skeletons were constructed from the simple and readily available materials enaminone, 5-aminopyrazole, and 1,4-dithiane-2,5-diol. Furthermore, a novel 1,4-dithiane-2,5-diol reaction mode has been developed through a double-dipole-reversal process induced by iodine that results in the formation of six new bonds and two new rings in a one-pot reaction. This method shows good substrate compatibility, and the products can be further modified with a variety of pharmaceuticals. Additionally, this novel skeleton exhibits good fluorescence properties in solution, enabling bright and stable green fluorescence imaging in HeLa cells.

RESUMEN

A biliary stricture is an abnormal narrowing in the ductal drainage system of the liver. There are many etiologies of biliary stricture, the most common and ominous of which is malignancy, either primary or metastatic.It is difficult to obtain pathological tissue of the terminal end of the common bile duct. A 72-year-old woman, complained of abdominal pain for 2 months, underwent cholecystectomy for acute cholecystitis 11 years ago. Abdominal CT and MRI examination revealed soft tissue occupation (12*8 mm) in the duodenal papillary area, and endoscopic ultrasonography revealed a hypoechoic lesion (11.1*10.7 mm) in the ampulla. We performed ERCP, and intraoperative biliary cell brushing on the patient, but no positive pathological results were obtained. We further performed novel 9F digital single operator cholangioscopy system (DSOC) (eyeMAX, Micro-Tech, Nanjing, China) and observed intraoperative hyperemia and edema of the mucosa in the terminal end of the common bile duct, presenting fish-like changes with mucous attachment and clear lesion boundaries. The pathological results suggested cholangiocarcinoma.

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Natural killer cell-derived extracellular vesicles (NK-EVs) are being investigated as cancer biotherapeutics. They possess unique properties as cytotoxic nanovesicles targeting cancer cells and as immunomodulatory communicators. A scalable biomanufacturing workflow enables the production of large quantities of high-purity NK-EVs to meet the pre-clinical and clinical demands. The workflow employs a closed-loop hollow-fiber bioreactor, enabling continuous production of NK-EVs from the NK92-MI cell line under serum-free, xeno-free, feeder-free, and antibiotic-free conditions in compliance with Good Manufacturing Practices standards. This protocol-driven study outlines the biomanufacturing workflow for isolating NK-EVs using size-exclusion chromatography, ultrafiltration, and filter-based sterilization. Essential NK-EV product characterization is performed via nanoparticle tracking analysis, and their functionality is assessed through a validated cell viability-based potency assay against cancer cells. This scalable biomanufacturing process holds significant potential to advance the clinical translation of NK-EV-based cancer biotherapeutics by adhering to best practices and ensuring reproducibility.

Asunto(s)

Vesículas Extracelulares , Células Asesinas Naturales , Humanos , Vesículas Extracelulares/química , Flujo de Trabajo , Reactores Biológicos , Neoplasias/patología , Cromatografía en Gel/métodos , Línea Celular Tumoral

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The intricate relationship between bile acid (BA) metabolism, M2 macrophage polarization, and hepatitis B virus-hepatocellular carcinoma (HBV-HCC) necessitates a thorough investigation of ACSL4's (acyl-CoA synthetase long-chain family member 4) role. This study combines advanced bioinformatics and experimental methods to elucidate ACSL4's significance in HBV-HCC development. Using bioinformatics, we identified differentially expressed genes in HBV-HCC. STRING and gene set enrichment analysis analyses were employed to pinpoint critical genes and pathways. Immunoinfiltration analysis, along with in vitro and in vivo experiments, assessed M2 macrophage polarization and related factors. ACSL4 emerged as a pivotal gene influencing HBV-HCC. In HBV-HCC liver tissues, ACSL4 exhibited upregulation, along with increased levels of M2 macrophage markers and BA. Silencing ACSL4 led to heightened farnesoid X receptor (FXR) expression, reduced BA levels, and hindered M2 macrophage polarization, thereby improving HBV-HCC conditions. This study underscores ACSL4's significant role in HBV-HCC progression. ACSL4 modulates BA-mediated M2 macrophage polarization and FXR expression, shedding light on potential therapeutic targets and novel insights into HBV-HCC pathogenesis.

RESUMEN

The emergence of immunotherapy, particularly immune checkpoint inhibitors (ICIs), represents a groundbreaking approach to treating gastric cancer (GC). However, the prognosis of GC patients receiving ICI treatment is influenced by various factors. This manuscript identified sarcopenia and myosteatosis as inde-pendent prognostic factors impacting the outcomes of GC patients treated with ICIs. Additionally, this study introduced a visual predictive model to estimate the prognosis of GC patients. If confirmed by further studies, this observation could provide valuable insights to propel the advancement of personalized clinical medicine and the integration of precision medicine practices.

Asunto(s)

Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Neoplasias Gástricas , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/terapia , Neoplasias Gástricas/patología , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/métodos , Inmunoterapia/efectos adversos , Resultado del Tratamiento , Pronóstico , Medicina de Precisión/métodos , Sarcopenia/inmunología , Sarcopenia/inducido químicamente

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The rising prevalence of Lyme disease (LD) in North America and Europe has emerged as a pressing public health concern. Despite the availability of veterinary LD vaccines, no vaccine is currently available for human use. Outer surface protein C (OspC) found on the outer membrane of the causative agent, Borrelia burgdorferi, has been identified as a promising target for LD vaccine development due to its sustained expression during mammalian infection. However, the efficacy and immunological mechanisms of LD vaccines solely targeting OspC are not well characterized. In this study, we developed an attenuated Vaccinia virus (VV) vectored vaccine encoding type A OspC (VV-OspC-A). Two doses of the VV-OspC-A vaccine conferred complete protection against homologous B. burgdorferi challenge in mice. Furthermore, the candidate vaccine also prevented the development of carditis and lymph node hyperplasia associated with LD. When investigating the humoral immune response to vaccination, VV-OspC-A was found to induce a robust antibody response predominated by the IgG2a subtype, indicating a Th1-bias. Using a novel quantitative flow cytometry assay, we also determined that elicited antibodies were capable of inducing antibody-dependent cellular phagocytosis in vitro. Finally, we demonstrated that VV-OspC-A vaccination generated a strong antigen-specific CD4+ T-cell response characterized by the secretion of numerous cytokines upon stimulation of splenocytes with OspC peptides. This study suggests a promising avenue for LD vaccine development utilizing viral vectors targeting OspC and provides insights into the immunological mechanisms that confer protection against B. burgdorferi infection.

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BACKGROUND: The majority of esophageal subepithelial lesions originating from the muscularis propria (SEL-MPs) are benign in nature, although a subset may exhibit malignant characteristics. Conventional endoscopic resection techniques are time-consuming and lack efficacy for small SEL-MPs. AIM: To evaluate the efficacy and safety of ligation-assisted endoscopic submucosal resection (ESMR-L) following unroofing technique for small esophageal SEL-MPs. METHODS: From January 2021 to September 2023, 17 patients diagnosed with esophageal SEL-MPs underwent ESMR-L following unroofing technique at the endoscopy center of Shenzhen People's Hospital. Details of clinicopathological characteristics and clinical outcomes were collected and analyzed. RESULTS: The mean age of the patients was 50.12 ± 12.65 years. The mean size of the tumors was 7.47 ± 2.83 mm and all cases achieved en bloc resection successfully. The average operation time was 12.2 minutes without any complications. Histopathology identified 2 Lesions (11.8%) as gastrointestinal stromal tumors at very low risk, 12 Lesions (70.6%) as leiomyoma and 3 Lesions (17.6%) as smooth muscle proliferation. No recurrence was found during the mean follow-up duration of 14.18 ± 9.62 months. CONCLUSION: ESMR-L following roofing technique is an effective and safe technique for management of esophageal SEL-MPs smaller than 20 mm, but it cannot ensure en bloc resection and may require further treatment.

Asunto(s)

Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Leiomioma , Humanos , Resección Endoscópica de la Mucosa/métodos , Resección Endoscópica de la Mucosa/efectos adversos , Persona de Mediana Edad , Femenino , Masculino , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Adulto , Ligadura/métodos , Resultado del Tratamiento , Leiomioma/cirugía , Leiomioma/patología , Tempo Operativo , Estudios Retrospectivos , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/patología , Mucosa Esofágica/cirugía , Mucosa Esofágica/patología , Mucosa Esofágica/diagnóstico por imagen , Anciano , Esófago/cirugía , Esófago/patología , Esofagoscopía/métodos , Esofagoscopía/efectos adversos

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke is an acute central nervous system disease that poses a threat to human health. It induces a series of severe pathological mechanisms, ultimately leading to neuronal cell death in the brain due to local ischemia and hypoxia. Buyang Huanwu decoction (BYHWD), as a representative formula for treating ischemic stroke, has shown good therapeutic effects in stroke patients. AIM OF THE STUDY: This study aimed to explore the mechanism of BYHWD in promoting neural remodeling after ischemic stroke from the perspective of neuronal synaptic plasticity, based on the cAMP/PKA/CREB signaling pathway. MATERIALS AND METHODS: A modified suture technique was employed to establish a rat model of MCAO. The rats were divided into sham, model, and BYHWD (20 g/kg) groups. After the corresponding intervention, rat brains from each group were collected. TMT quantitative proteomics technology was employed for the research. Following proteomics studies, we investigated the mechanism of BYHWD in the intervention of ischemic stroke through animal experiments and cell experiments. The experimental animals were divided into sham, model, and BYHWD (5 g/kg, 10 g/kg, and 20 g/kg) groups. Infarct volume and severity of brain injury were measured by TTC staining. HE staining was utilized to evaluate alterations in tissue morphology. The Golgi staining was used to observe changes in cell body, dendrites, and dendritic spines. Transmission electron microscopy was used to observe the ultrastructure of synapses in the cortex and hippocampus. TUNEL staining was conducted to identify apoptotic neurons. Meanwhile, a stable and reliable (OGD/R) SH-SY5Y cell model was established. The effect of BYHWD-containing serum on SH-SY5Y cell viability was measured by CCK-8 kit. The apoptosis situation of SH-SY5Y cells was determined by Annexin V-FITC/PI. Immunofluorescence was employed to measure the fluorescence intensity of synaptic-related factors Syt1, Psd95, and Syn1. Synaptic plasticity pathways were assessed by using RT-qPCR and Western blot to determine the expression levels of cAMP, Psd95, Prkacb, Creb1/p-Creb1, BDNF, Shank2, Syn1, Syt1, Bcl-2, Bcl-2/Bax mRNA and proteins. RESULTS: After treatment with BYHWD, notable alterations were detected in the signaling pathways linked to synaptic plasticity and the cAMP signaling pathway-related targets among the intervention targets. This trend of change was also reflected in other bioinformatics analyses, indicating the important role of synaptic plasticity changes before and after modeling and drug intervention. The results of vivo and vitro experiments showed that BYHWD improved local pathological changes, and reduced cerebral infarct volume, and neurological function scores in MCAO rats. It increased dendritic spine density, improved synaptic structural plasticity, and had a certain neuroprotective effect. BYHWD increased the postsynaptic membrane thickness, synaptic interface curvature, and synaptic quantity. 10% BYHWD-containing serum was determined as the optimal concentration for treatment. 10% BYHWD-containing serum significantly reduced the overall apoptotic rate of (OGD/R) SH-SY5Y cells. Immunofluorescence experiments demonstrated that 10% BYHWD-containing serum could improve synaptic plasticity and increase the relative expression levels of synaptic-related proteins Syt1, Psd95, and Syn1. BYHWD and decoction-containing serum upregulated the mRNA and protein expression levels in (OGD/R) SH-SY5Y cells and MCAO rats, suggesting its ability to improve damaged neuronal synaptic plasticity and enhance transmission efficiency, which might be achieved through the regulation of the cAMP/PKA/CREB pathway. CONCLUSIONS: This study may provide a basis for clinical medication by elucidating the underlying experimental evidence for the promotion of neural plasticity after ischemic stroke by BYHWD.

Asunto(s)

Proteína de Unión a Elemento de Respuesta al AMP Cíclico , AMP Cíclico , Medicamentos Herbarios Chinos , Accidente Cerebrovascular Isquémico , Plasticidad Neuronal , Ratas Sprague-Dawley , Transducción de Señal , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Plasticidad Neuronal/efectos de los fármacos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Masculino , AMP Cíclico/metabolismo , Ratas , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Modelos Animales de Enfermedad , Fármacos Neuroprotectores/farmacología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico

RESUMEN

Broadband spectrum detectors exhibit great promise in fields such as multispectral imaging and optical communications. Despite significant progress, challenges like materials instability in such devices, complex manufacturing process, and high cost still hinder their further application. Here, we present a method that achieves broadband spectral detection by impurity-level in SrSnO3. We report over 500 mA/W photoresponsivity at 275 nm (ultraviolet C solar-bind) and 367 nm (ultraviolet A) and ∼60 mA/W photoresponsivity at 532 and 700 nm (visible) with a voltage bias of -5 V. Further transport and photoluminescence results reveal a new phase transition at 88 K, which would significantly affect the impurity level of the La-doped SrSnO3 film, indicating that the broadband response attributes to the impurity levels and mutual interactions. Additionally, the photodetector demonstrates excellent robustness and stability under repeated tests and prolonged exposure in air. These findings show the potential of SrSnO3 as a material for photodetectors and propose a method to achieve broadband spectrum detection, creating new possibility for the development of single-phase, low-cost, simple structure, and high-efficiency photodetectors.

RESUMEN

The intestinal barrier maintained by various types of columnar epithelial cells, plays a crucial role in regulating the interactions between the intestinal contents (such as the intestinal microbiota), the immune system, and other components. Dysfunction of the intestinal mucosa is a significant pathophysiological mechanism and clinical manifestation of inflammatory bowel disease (IBD). However, current therapies for IBD primarily focus on suppressing inflammation, and no disease-modifying treatments specifically target the epithelial barrier. Given the side effects associated with chronic immunotherapy, effective alternative therapies that promote mucosal healing are highly attractive. In this review, we examined the function of intestinal epithelial barrier function and the mechanisms of behind its disruption in IBD. We illustrated the complex process of intestinal mucosal healing and proposed therapeutic approaches to promote mucosal healing strategies in IBD. These included the application of stem cell transplantation and organ-like tissue engineering approaches to generate new intestinal tissue. Finally, we discussed potential strategies to restore the function of the intestinal barrier as a treatment for IBD.

RESUMEN

BACKGROUND: Hyperuricemia (HUA) is a public health concern that needs to be solved urgently. The lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA; however, its underlying metabolic regulation remains unclear. AIM: To explore the underlying mechanisms of Poecilobdella manillensis in HUA based on modulation of the gut microbiota and host metabolism. METHODS: A mouse model of rapid HUA was established using a high-purine diet and potassium oxonate injections. The mice received oral drugs or saline. Additionally, 16S rRNA sequencing and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry-based untargeted metabolomics were performed to identify changes in the microbiome and host metabolome, respectively. The levels of uric acid transporters and epithelial tight junction proteins in the renal and intestinal tissues were analyzed using an enzyme-linked immunosorbent assay. RESULTS: The protein extract of Poecilobdella manillensis lyophilized powder (49 mg/kg) showed an enhanced anti-trioxypurine ability than that of allopurinol (5 mg/kg) (P < 0.05). A total of nine bacterial genera were identified to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder, which included the genera of Prevotella, Delftia, Dialister, Akkermansia, Lactococcus, Escherichia_Shigella, Enterococcus, and Bacteroides. Furthermore, 22 metabolites in the serum were found to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder, which correlated to the Kyoto Encyclopedia of Genes and Genomes pathways of cysteine and methionine metabolism, sphingolipid metabolism, galactose metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. Correlation analysis found that changes in the gut microbiota were significantly related to these metabolites. CONCLUSION: The proteins in Poecilobdella manillensis powder were effective for HUA. Mechanistically, they are associated with improvements in gut microbiota dysbiosis and the regulation of sphingolipid and galactose metabolism.

Asunto(s)

Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Hiperuricemia , Sanguijuelas , Animales , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/sangre , Hiperuricemia/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Masculino , Sanguijuelas/microbiología , Ácido Úrico/sangre , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/microbiología , Metabolómica/métodos , ARN Ribosómico 16S/genética , Humanos , Disbiosis , Metaboloma/efectos de los fármacos

RESUMEN

Background: Pulmonary vein stenosis (PVS) continues to be a major complication after surgical repair of total anomalous pulmonary venous connection (TAPVC). Recent studies suggest that the morphology of pulmonary venous confluence and the left atrium (LA) is associated with PVS. However, there are limited data on the prognostic value of integrating quantitative confluence-atrial morphology into risk stratification. Objectives: This study sought to evaluate the prognostic impact of novel imaging metrics derived from 3-dimensional (3D) computed tomography angiography (CTA) modeling on postsurgical PVS (PPVS) in the supracardiac TAPVC (sTAPVC) setting. Methods: Patients undergoing sTAPVC repair in 2017 to 2022 from 3 centers were retrospectively reviewed. Study investigators developed 3D CTA modeled geometric features to quantify confluence-atrial morphology that were analyzed with regard to PPVS. Results: Of the 162 patients (median age 61 days; 55% having preoperative pulmonary venous obstruction [prePVO]) included, 47 (29%) with PPVS at a median of 1.5 months ([quartile 1-quartile 3: 1.5-3.0 months]). In the univariable analysis, the indexed total volume of the LA and confluence (iTVLC) and the ratio of the corresponding confluence length to the mean distance between the LA and confluence (CCL/mDBLC ratio) were significantly associated with PPVS. In a multivariable model adjusting for prePVO and age, the iTVLC and CCL/mDBLC ratio independently predicted PPVS (HR: 1.15; 95% CI: 1.06-1.25; and HR: 1.20; 95% CI: 1.08-1.35, respectively, all P < 0.01). Specifically, an iTVLC ≥20 cm3/m2 and a CCL/mDBLC ratio ≥7.7 were significantly associated with a reduced risk of PPVS. Conclusions: Quantification of 3D confluence-atrial morphology appears to offer a deeper and better metric to predict PPVS in patients with sTAPVC.

RESUMEN

Soft actuators made of soft materials cannot generate precisely efficient output forces compared to rigid actuators. It is a promising strategy to equip soft actuators with variable stiffness modules of layer jamming mechanism, which could increase their stiffness as needed. Inspired by the gecko's the array of setae, bionic adhesive flaps with inclined micropillars are applied in layer jamming mechanism. In this paper, after the manufacturing process of the layer jamming actuator based on the bionic adhesive flaps is described, the equivalent stiffness models of the whole actuator are established in the unjammed and jammed states. And the shear adhesive force of a single micropillar is calculated based on the Kendall viscoelastic band model. The finite element simulation results of two bionic adhesive flaps show that the interlaminar shear stress and stiffness increase with the increase of pressure. The measurement of shear adhesive force show that the critical shear adhesive force of the bionic adhesive material is 3.2 times that of polyethylene terephthalate (PET) material, and exhibit the ability of anisotropic adhesion behavior. The variable stiffness performance of the layer jamming actuator based on bionic adhesive flaps is evaluated by three test methods, and the max stiffness reaches 8.027 N mm-1, which is 1.5 times higher than the stiffness of the layer jamming actuator based on the PET flaps. All results of simulation and experiment effectively verify the validity and superiority of applying the bionic adhesive flaps to the layer jamming mechanism to enhance the stiffness.

Asunto(s)

Adhesivos , Materiales Biomiméticos , Biónica , Diseño de Equipo , Animales , Adhesivos/química , Análisis de Elementos Finitos , Lagartos/fisiología , Simulación por Computador , Robótica/instrumentación , Biomimética/métodos , Tereftalatos Polietilenos/química , Estrés Mecánico

RESUMEN

BACKGROUND: Multiple endocrine neoplasias (MENs) are a group of hereditary diseases involving multiple endocrine glands, and their prevalence is low. MEN type 1 (MEN1) has diverse clinical manifestations, mainly involving the parathyroid glands, gastrointestinal tract, pancreas and pituitary gland, making it easy to miss the clinical diagnosis. CASE SUMMARY: We present the case of a patient in whom MEN1 was detected early. A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the hospital. Blood tests at admission revealed hypercalcemia and hypophosphatemia, and emission computed tomography of the parathyroid glands revealed a hyperfunctioning parathyroid lesion. Gastroscopy findings suggested a duodenal bulge and ulceration. Ultrasound endoscopy revealed a hypoechoic lesion in the duodenal bulb. Further blood tests revealed elevated levels of serum gastrin. Surgery was performed, and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal bulbectomy. The time from onset to the definitive diagnosis of MEN1 was only approximately 1 year. CONCLUSION: For patients who present with gastrointestinal symptoms accompanied by hypercalcemia and hypophosphatemia, clinicians need to be alert to the possibility of MEN1.

Asunto(s)

Hipercalcemia , Neoplasia Endocrina Múltiple Tipo 1 , Neoplasias de las Paratiroides , Paratiroidectomía , Humanos , Neoplasia Endocrina Múltiple Tipo 1/cirugía , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico , Neoplasia Endocrina Múltiple Tipo 1/complicaciones , Neoplasia Endocrina Múltiple Tipo 1/patología , Masculino , Neoplasias de las Paratiroides/cirugía , Neoplasias de las Paratiroides/diagnóstico , Neoplasias de las Paratiroides/patología , Neoplasias de las Paratiroides/complicaciones , Persona de Mediana Edad , Hipercalcemia/diagnóstico , Hipercalcemia/etiología , Hipercalcemia/sangre , Adenoma/cirugía , Adenoma/diagnóstico , Adenoma/patología , Adenoma/sangre , Neoplasias Duodenales/cirugía , Neoplasias Duodenales/diagnóstico , Neoplasias Duodenales/patología , Hipofosfatemia/etiología , Hipofosfatemia/diagnóstico , Dolor Abdominal/etiología , Dolor Abdominal/diagnóstico , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/sangre , Tumores Neuroendocrinos/patología , Diarrea/etiología , Diarrea/diagnóstico , Detección Precoz del Cáncer/métodos , Gastroscopía , Resultado del Tratamiento

Asunto(s)

Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Humanos , Resección Endoscópica de la Mucosa/métodos , Neoplasias Esofágicas/cirugía , Masculino , Tracción/métodos , Persona de Mediana Edad , Anciano

RESUMEN

BACKGROUND: Pancreatic surgery has long been burdened with high postoperative morbidity. Early mobilization has been advocated to prevent complications and improve functional capacity. However, there is a lack of high-quality evidence supporting how to implement early mobilization and its independent impact on postoperative outcomes. The aim of this study was to investigate the effectiveness of implementing early mobilization in reducing postoperative complications and enhancing recovery in patients undergoing pancreatic surgery. METHODS: We conducted a single-blind, randomized trial in patients who underwent pancreatic surgery in a tertiary hospital in China. Eligible participants were randomly assigned to either the control group or the intervention group. Patients in the control group received usual care, whereas those in the intervention group received the early enforced mobilization protocol. The protocol consisted of 2 key components: professional assistance with the first ambulation on postoperative day 1 and family-involved supervision to achieve daily walking goals. The primary outcome was postoperative complications within 30 days, measured by the Comprehensive Complication Index. Secondary outcomes were postoperative mobilization, time to recovery of gastrointestinal function, postoperative pulmonary complications, pancreatic surgery-specific complications, patient-reported outcome measures, and 30-day readmission and mortality. RESULTS: A total of 135 patients were enrolled: 67 in the intervention group and 68 in the control group. The median Comprehensive Complication Index was not statistically significant between groups (mean difference -1.7; 95% confidence interval -8.7 to 0). Patients in the intervention group had earlier first ambulation postoperatively, walked greater distances on postoperative days 1-7, and had earlier time to first defecation. Trends for improvement in patient-reported outcomes showed that scores of Quality of Recovery 15 at postoperative day 3, physical function of Quality of Life Questionnaire C30 at postoperative day 7, and global quality of life at postoperative day 30 were significantly greater in the intervention group. There was no between-group difference in other domains of the Quality of Life Questionnaire C30 or other secondary outcome measures. CONCLUSION: Early enforced mobilization intervention did not reduce postoperative complications of patients undergoing pancreatic surgery, but it can enhance postoperative mobilization and improve the recovery of gastrointestinal function and patient-perceived quality of recovery.

Asunto(s)

Ambulación Precoz , Pancreatectomía , Complicaciones Posoperatorias , Humanos , Masculino , Persona de Mediana Edad , Femenino , Método Simple Ciego , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Pancreatectomía/efectos adversos , Pancreatectomía/métodos , Anciano , Adulto , Recuperación de la Función , China , Resultado del Tratamiento , Recuperación Mejorada Después de la Cirugía

RESUMEN

BACKGROUND: Gastric venous bleeding is one of the most common adverse events in liver cirrhosis. The therapeutic effect of isolated gastric varices is relatively clear. However, there is no appropriate clinical and endoscopic treatment for extensive variceal bleeding in the gastric fundus and body. METHODS: In this patient with non-isolated gastric varices, we decided to perform endoscopic multi-point ligation of the obvious varices in the gastric fundus and body. RESULTS: In this patient, endoscopic treatment of gastric varices with bleeding after surgery achieved a significant therapeutic effect. Reexamination of gastroscopy at 3 months after operation showed that multiple scars were formed in the gastric fundus and fundus, and no obvious varices were found. CONCLUSIONS: For patients with non-isolated gastric varices, endoscopic multi-point ligation is a safe and effective treatment option for the varices with obvious gastric fundus and body.

RESUMEN

Natural killer cell-derived extracellular vesicles (NK-EVs) are candidate biotherapeutics against various cancers. However, standardised potency assays are necessary for a reliable assessment of NK-EVs' cytotoxicity. This study aims to thoroughly evaluate a highly sensitive resazurin phenoxazine-based cell viability potency assay (measurement of the cellular redox metabolism) for quantifying the cytotoxicity of NK-EVs against leukaemia K562 cells (suspension model) and breast cancer MDA-MB-231 cells (adherent model) in vitro. The assay was evaluated based on common analytical parameters setforth by regulatory guidelines, including specificity, selectivity,accuracy, precision, linearity, range and stability. Our results revealed that this resazurin-based cell viability potency assay reliably and reproducibly measured a dose-response of NK-EVs' cytotoxic activity against both cancer models. The assay showed precision with 5% and 20% variation for intra-run and inter-run variability. The assay signal showed specificity and selectivity of NK-EVs against cancer target cells, as evidenced by the diminished viability of cancer cells following a 5-hour treatment with NK-EVs, without any detectable interference or background. The linearity analysis of target cancer cells revealed strong linearity for densities of 5000 K562 and 1000 MDA-MB-231 cells per test with a consistent range. Importantly, NK-EVs' dose-response for cytotoxicity showed a strong correlation (|ρ| ∼ 0.8) with the levels of known cytotoxic factors associated with the NK-EVs' corona (FasL, GNLY, GzmB, PFN and IFN-γ), thereby validating the accuracy of the assay. The assay also distinguished cytotoxicity changes in degraded NK-EVs, indicating the ability of the assay to detect the potential loss of sample integrity. Compared to other commonly reported bioassays (i.e., flow cytometry, cell counting, lactate dehydrogenase release assay, DNA-binding reporter assay and confluence assay), our results support this highly sensitive resazurin-based viability potency assay as a high-throughput and quantitative method for assessing NK-EVs' cytotoxicity against both suspension and adherent cancer models for evaluating NK-EVs' biotherapeutics.